Tho existence of effects induced in biological systems by exposure to weak, extremely low frequency (ELF) electromagnetic fields (EMFs) is now becoming generally accepted within the scientific community. This fact, coupled with epidemiologic data which suggest the possible involvement of such weak EMFs in the incidence of leukemias and other cancers, has raised interest in the interactions of fields with living organisms. The cell- field interaction mechanism, however, is not understood. The research described in this proposal focuses on the investigation and characterization of the mechanisms by which cells detect, and respond, to weak, externally-impressed fields, while discriminating against intense endogenous thermal noise fields. Most of the proposed research will be conducted using mammalian cultured cells as the target of EMF exposure, primarily to applied 60 Hz, sinusoidal magnetic fields. The specific activity of the enzyme ornithine decarboxylase will serve as the biological endpoint for these studies. The work will consist of a series of experiments directed toward three major goals: (I) Preliminary studies have established that cellular detection of EMFs involves at least two important time scales: a rather short "sensing" interval, and a somewhat longer "memory" time. The temporal detection parameters will be thoroughly characterized, and the resultant data used to describe the cell-field interaction mechanism. (2) Experiments will examine the dose-response characteristics that determine cellular response to applied EMFs. This will include an examination of amplitude thresholds for bio-response at various field frequencies, and an examination of what constitutes a "minimum effective dose" of field exposure. (3) Applied ELF noise fields with electric field amplitudes 100-1000 times smaller than those calculated for thermal noise fields have been shown to reduce, or to eliminate, the typical cellular response to applied 60 Hz magnetic fields. A series of EMF exposures will be conducted to explore the crucial differences, in terms of such inhibitory effects, between such externally impressed noise fields and the endogenous thermal noise fields.